iκbα

B I09, an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells., an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells., an IRE-1 RNase inhibitor with an IC50 of 1230 nM, inhibits splicing of XBP1 mRNA in human WaC3 cells and expression of xbp-1 in LPS-stimulated B cells. B I09 can be used to simulate the defects of XBP-1 in CLL cells.

1. Sanggenon C (Sanggenone C) inhibits tumor cellular proteasomal activity and cell viability, via induction of cell cycle arrest and cell death , inhibiting the proteasome function. 2. Sanggenon C and O inhibited NO production and iNOS expression by suppressing NF-κB activity and IκBα activation; inhibited TNF-alpha -stimulated PMN-HSC adhesion and expression of VCAM-1 by suppressing the activation of NF-kappaB.

Indole-3-carbinol (I3C), a naturally occurring, orally available cleavage product of the glucosinolate glucobrassicanin, inhibits NF-κB and IκBα kinase activation.

Schisantherin A (Wuweizi ester-A) is a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent.

Bay 11-7085 can irreversibly inhibit the IκBα phosphorylation induced by TNFα (IC50: 10 μM).

JSH-23, an NF-κB inhibitor（IC50= 7.1 μM）, suppresses the transcriptional activity.

BAY 11-7082 (BAY 11-7821) is an NF-κB inhibitor that inhibits TNFα-induced IκBα phosphorylation (IC50=10 μM). BAY 11-7082 is also an inhibitor of the ubiquitin-specific proteases USP7 and USP21 (IC50=0.19 0.96 μM).

Wedelolactone (IKK Inhibitor II) inhibits NF-κB-mediated gene transcription in cells by blocking the phosphorylation and degradation of IκBα.

IMD-0354 (IKK2 Inhibitor V) is an IKKβ inhibitor and inhibits IκBα phosphorylation in NF-κB pathway.

Narasin (sodium salt) (HainanMycin) induces tumor necrosis factor-related apoptosis-induced ligand (TRAIL)-mediated apoptosis by ER stress in glioma cells and inhibits NF-κB signaling by suppressing the phosphorylation of IκBα.

Potent inhibitor of NF-κB activation (IC50 = 85 nM); decreases IκBα phosphorylation. Attenuates LPS-induced nitric oxide production and expression of TNF-α, IL-6 and MCP. Suppresses proliferation of HeLa and HCT116 cells. Anti-inflammatory and antitumor. Hu et al (2007) Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases. Chem.Biol. 14 764 PMID:17656313 |Johnson et al (2012) Myxobacteria versus sponge-derived alkaloids: the bengamide family identified as potent immune modulating agents by scrutiny of LC-MS/ELSD libraries. Bioorg.Med.Chem. 20 4348 PMID:22705020 |Kinder et al (2001) Synthesis and antitumor activity of ester-modified analogues of bengamide B. J.Med.Chem. 44 3692 PMID:11606134

PR 39 (porcine) acetate is a noncompetitive, reversible and allosteric proteasome inhibitor. PR 39 (porcine) acetate reversibly binds to the α7 subunit of the proteasome and blocks degradation of NF-κB inhibitor IκBα by the ubiquitin-proteasome pathway.

Gliotoxin-13C13is intended for use as an internal standard for the quantification of gliotoxin by GC- or LC-MS. Gliotoxin is an immunosuppressive mycotoxin produced by pathogenic strains ofAspergillusand other fungi with diverse biological activities.1,2,3,4,5,6,7,8It inhibits 20S proteasomal chymotrypsin activity (IC50= 10 μM), blocking the degradation of IκBα and preventing the activation of NF-κB.2,3Gliotoxin induces apoptosis in monocytes and dendritic cells and reduces phagocytosis by neutrophils.4,5It suppresses viral infection by Nipah and Hendra virus in HEK293T cells (IC50s = 149 and 579 nM, respectively).6Under reducing conditions, gliotoxin inhibits leukotriene A4hydrolase epoxide hydrolase activity, but not aminopeptidase activity, and leukotriene B4synthesis in neutrophils and monocytes.7

SH-5, an AKT inhibitor potentiates apoptosis and inhibits invasion through the suppression of anti-apoptotic, proliferative and metastatic gene products regulated by IκBα kinase activation.

IKKß-IN-124 is an allosteric inhibitor of IκBα phosphorylation and NF-κB transcriptional activity through selective capture of the inactive conformation and hence blockade of IKKβ S177/S181 phosphorylation.

Rubiadin-1-methyl ether (Rubiadin 1-methyl ether) is a natural product.It inhibits osteoclastic bone resorption via inhibition on the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decrease in the nuclear translocation of p65.

TNF-α-IN-11 (Compound 10) is a TNF-α inhibitor exhibiting a dissociation constant (K D) of 12.06 μM. By binding to TNF-α, it impedes TNF-α-induced caspase activation and the NF-κB signaling pathway. Additionally, it suppresses the phosphorylation of IκBα and the nuclear migration of NF-κB p65. This compound is utilized in the study of TNF-α-mediated autoimmune diseases [1].

Chicanine has anti-inflammatory activity in macrophages by down-regulating LPS-induced inflammatory cytokines in IκBα±/MAPK/ERK signaling pathways.

1. Cucurbitacin IIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. 2. Cucurbitacin IIb exhibits its anti-inflammatory activity through modula

NSC663627 is an IκBα phosphorylation inhibitor.

AKCI is a PPI inhibitor that acts by targeting the AURKC-IκBα interaction.

GS143 is a selec­tive IκBα ubiquitination inhibitor with an IC50 of 5.2 μM for SCFβTrCP1-mediated IκBα ubiquitylation. GS143 sup­presses NF-κB acti­va­tion and tran­scrip­tion of tar­get genes and does not inhibit proteasome activity. GS143 has anti-asthm

Anti-inflammatory agent 6 exhibits anti-inflammatory potential by blocking the phosphorylation of Iκb kinase α/β (IKKα/β), IκBα and nuclear factor kB p65 (NF-κb p65), which are key controllers of inflammation.

Anemarsaponin B has anti-inflammatory effect in LPS-treated RAW 264.7macrophages, the effect is associated with the inhibition of NF-κB transcriptional activity, possibly via the p38 MAP kinase pathway. Anemarsaponin B can inhibit PAF-induced rabbit platelet aggregation in vitro.

1-Dehydro-[10]-gingerdione inhibits IKKβ activity by targeting its activation loop, thereby preventing IKKβ-mediated phosphorylation of IκBα in macrophages stimulated by agonists. Furthermore, this compound suppresses LPS-induced NF-κB transcriptional activity, highlighting its potential in research related to NF-κB-associated inflammation and autoimmune disorders [1].

NF-κB-IN-4 (compound 17) is a potent inhibitor of NF-κB pathway which can cross blood brain barrier (BBB). NF-κB-IN-4 shows potential anti-neuroinflammatory activity with low toxicity which can be used for the research of neuroinflammation related diseases. NF-κB-IN-4 can block the IκBα activation and phosphorylation, reduce NLRP3 expression, therefore inhibiting NF-κB activation [1].

Urolithin B is one of the gut microbial metabolites of ellagitannins and is found in diverse plant foods, including pomegranates, berries, walnuts, tropical fruits, and medicinal herbs. Urolithin B inhibits NF-κB activity by reducing the phosphorylation and degradation of IκBα, and suppresses the phosphorylation of JNK, ERK, and Akt, and enhances the phosphorylation of AMPK. Urolithin B is also a regulator of skeletal muscle mass. Urolithin B has anti-inflammatory and antioxidant effects.

Eurycomalactone is a natural product isolated from Eurycoma longifolia Jack., acts as a potent NF-κB inhibitor( IC50 of 0.5 μM). Eurycomalactone inhibits protein synthesis, depletes cyclin D1, but does not affect TNFα-induced degradation of IκBα or the phosphorylation of IKKα/β and IκBα.

Glaucine has antitussive, antioxidative potential and antiviral activities, it may be an anti-arthritic agent, it can enhance LPS and zymosan-induced IL-10 production. Glaucine can inhibit the migration and invasion of human breast cancer cells by MMP-9 i

(±)-Nutlin-3 blocks the interaction of p53 with its negative regulator Mdm2 (IC50 = 90 nM), inducing the expression of p53-regulated genes and blocking the growth of tumor xenografts in vivo. CAY10682 is a pyrrolo[3,4c]pyrazole derivative that inhibits the p53-Mdm2 interaction as potently as (±)-nutlin-3 (Ki = 83 nM) and also dose-dependently reduces activation of the NF-κB pathway. It specifically prevents phosphorylation of IκBα by the kinases IKKα, IKKβ, and IKK (IC50s = 80.5, 78.2, and 57.1 μM, respectively). CAY10682 blocks the growth of cancer cells in vitro (IC50s = 2-6 μM) and inhibits the growth of A549 cell xenografts in mice without significantly reducing body weight.

Inactivation of the tumor suppressor p53 commonly coincides with increased signaling through NF-κB in cancer. CAY10681 is a dual modulator of p53-MDM2 interaction and NF-κB signaling. It potently binds MDM2 (Ki = 250 nM), reducing MDM2-mediated turnover of p53. CAY10681 also inhibits phosphorylation of IκBα and dose-dependently reduces nuclear accumulation of p65. It blocks the proliferation of cancer cell lines (IC50s range from 33 to 37 μM). CAY10681 exhibits excellent oral bioavailability and inhibits tumor growth in A549 xenografts in nude mice.

Micheliolide(MCL) is a sesquiterpene lactone which inhibits various inflammatory response.

Antibacterial peptide. Stimulates angiogenesis and inhibits inflammatory responses by selectively blocking proteasome degradation of IκBα.

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM. Benpyrine tightly binds to TNF-α and blocks its interaction with TNFR1, with an IC50 value of 0.109 μM. Benpyrine has the potential for TNF-α mediated inflammatory and autoimmune disease research[1]. Benpyrine (5-20 μM; 14 hours; RAW264.7 cells) pretreatment results in a dose-dependent decrease in the phosphorylation of IκBα in RAW264.7 cells (stimulated with 10 ng/mL TNF-α or 1 μg/mL LPS). Benpyrine abolishes the TNF-α-induced nuclear translocation of NF-κB/p65 in RAW264.7 cells[1].Benpyrine only blocks cell death induced by TNF-αWT and Y119A, and increases the cell survival rate up to 80%. Benpyrine does not obviously affect L57A- and Y59L-induced cytotoxicity in L929 cells[1]. Benpyrine (25-50 mg/kg; oral gavage; daily; for 2 weeks; Balb/c mice) treatment significantly relieves the symptoms of collagen-induced arthritis. Benpyrine dose-dependently decreases the levels of proinflammatory cytokines, such as IFN-γ, IL-1β and IL-6, and increases the concentration of the anti-inflammatory cytokine IL-10[1].Endotoxemia murine model shows that Benpyrine (25 mg/kg) could attenuate TNF-α-induced inflammation, thereby reducing liver and lung injury[1]. [1]. Weiguang Sun, et al. Discovery of an Orally Active Small Molecule TNF-α Inhibitor. J Med Chem. 2020 Jul 15.

Cyclo(L-Pro-L-Val), a 2,5-diketopiperazine extracted from the fruits of Mycobacterium chiliolyticum AZ2 and Mycobacterium leprae, possesses anti-inflammatory activity and virulence activity against phytopathogenic microorganisms (e.g., R. fascians LMG 3605) and inhibits Gram-positive plant pathogens.Cyclo(L-Pro-L-Val) significantly inhibited IKKα phosphorylation and IκBα and NF-κB activation as well as iNOS and COX-2 activation in a concentration Cyclo(L-Pro-L-Val) significantly inhibited the phosphorylation of IKKα, IKKβ, IκBα, and NF-κB, as well as the activation of iNOS and COX-2 in a concentration-dependent manner, and is a potential therapeutic agent for the treatment of inflammation-related diseases.

Anti-osteoporosis agent-4 (Compound 11h) suppresses the differentiation of primary osteoclasts and attenuates RANKL-induced osteoclastogenesis. It effectively inhibits osteoclast formation, demonstrating an IC50 value of 358.29 nM, and impedes the activation of the PI3K/AKT and IκBα/NF-κB signaling pathways [1].

NF-κB-IN-11 (Compound 3i) is an inhibitor of NF-κB, effectively blocking TNF-α-induced NF-κB pathway activation and the nuclear translocation of NF-κB. It also reduces the expression levels of phospho-IKK, IκBα, and NF-κB p65. Demonstrating anti-inflammatory properties, NF-κB-IN-11 mitigates dextran sulfate sodium-induced colitis in mice and exhibits a maximum tolerated dose (MTD) exceeding 1852 mg/kg in acute toxicity assays when administered orally (p.o.) [1].

PR-39 TFA, a natural peptide rich in proline and arginine with antibacterial properties, acts as a noncompetitive, reversible, and allosteric inhibitor of the proteasome. It specifically attaches to the α7 subunit of the proteasome, preventing the degradation of the NF-κB inhibitor IκBα through the ubiquitin-proteasome pathway. Additionally, PR-39 TFA promotes angiogenesis, suppresses inflammatory responses, and notably decreases myocardial infarct size in mice [1] [2].